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We identified has_circ_0000437 from three pairs of clinical samples using a circRNA microarray and predicted the has_circ_0000437 sponge let-7f-5p using bioinformatics. We expanded the sample to confirm the expression, correlation, and diagnostic value of has_circ_0000437, let-7f-5p and RAS-like proto-oncogene B (RALB) in rheumatic valvular heart disease (RVHD). The effects of has_circ_0000437 and let-7f-5p on biological function were observed in hVICs cells. To explore the molecular pathogenesis of has_circ_0000437 in the RVHD process, the target binding protein RAS-like proto-oncogene B (RALB) of has_circ_0000437 was obtained using label-free mass spectrometry and parallel reaction monitoring. The influence of the has_circ_0000437\/let-7f-5p\/RALB axis on the expression of mitogen-activated protein kinase (MAPK)-related proteins in the inflammatory signaling pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) during RVHD was measured using Western blotting. We found that let-7f-5p was at low expression and negatively correlated with has_circ_0000437, which had a diagnostic value with an area under the curve of 0.998 after the combined diagnosis. Has_circ_0000437 and let-7f-5p had binding sites, and let-7f-5p alleviated the effect of has_circ_0000437 on the proliferation, migration, and cycle progression of hVICs. The inhibitory effect of has_circ_0000437 on hVICs apoptosis was diminished. Mechanism studies showed that has_circ_0000437 promotes the MAPK pathway through has_circ_0000437\/let-7f-5p\/RALB axis. These findings suggest that the has_circ_0000437\/let-7f-5p\/RALB axis promotes the MAPK pathway, proliferation, migration, and cycle progression in RVHD, inhibiting the apoptosis process, thereby promoting RVHD development. This pathway may suggest a target for RVHD diagnosis and treatment.<\/jats:p>","DOI":"10.1007\/s13577-025-01331-7","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T18:20:04Z","timestamp":1765822804000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hsa_circ_0000437 promotes the progression of rheumatic valvular heart disease by activating the mitogen-activated protein kinase signaling pathways after sponging let-7f-5p and targeting RAS-like proto-oncogene B"],"prefix":"10.1007","volume":"39","author":[{"given":"Linwen","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ni","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huoshun","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongjie","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinbo","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuying","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanggang","family":"Dan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guofeng","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3229-4790","authenticated-orcid":false,"given":"Lebo","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"issue":"1","key":"1331_CR1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.jacc.2022.09.050","volume":"81","author":"S Dougherty","year":"2023","unstructured":"Dougherty S, Okello E, Mwangi J, Kumar R. 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